The inhibition of metallo-beta-lactamase by thioxo-cephalosporin derivatives

Bioorg Med Chem Lett. 2004 Apr 5;14(7):1737-9. doi: 10.1016/j.bmcl.2004.01.047.

Abstract

The 8-thioxocephalosporins are poor substrates for the B. cereus metallo beta-lactamase (k(cat)/K(m)=61.4M(-1) s(-1)) and act as weak competitive inhibitors (K(i) approximately 700 microM). The hydrolysis product of thioxocephalosporin, a thioacid, also inhibits the enzyme competitively with a K(i)=96 microM, whereas the cyclic thioxo-piperazinedione, formed by intramolecular aminolysis of thioxocephalexin has a K(i) of 29 microM.

MeSH terms

  • Bacillus cereus / drug effects
  • Bacillus cereus / enzymology
  • Cephalosporins / chemistry*
  • Cephalosporins / metabolism
  • Cephalosporins / pharmacology
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / metabolism

Substances

  • Cephalosporins
  • Enzyme Inhibitors
  • beta-Lactamase Inhibitors
  • beta-Lactamases